New aminoglycoside antibiotics, sannamycin.

Deushi, Takeo; Iwasaki, Akio; Kamiya, Kazuhiro; Mizoguchi, Toshimi; Nakayama, Masahito; Itoh, Hisakatsu; Mori, Toshihito

doi:10.7164/antibiotics.32.1061

Cited by 24 publications

(3 citation statements)

References 6 publications

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“…Its increased activity against P. aeruginosa compared with that of fortimicin A also seems superior to those recently described for sannamycin A, sporaricin A, and istamycin B (3,4,11). A49759 was very active against the Enterobacteriaceae, other pseudomonads, acinetobacters, and the staphylococci.…”

Section: Discussionmentioning

confidence: 73%

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Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics

Jones¹,

Thornsberry²,

Barry³

et al. 1980

Antimicrob Agents Chemother

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O-Demethylfortimicin A (compound A49759) was tested against 445 bacteria, and the results were compared with thooe obtained with fortimicin A, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin. A49759 was found to be active and bactericidal against the Enterobacteriaceae, nonfermentative gram-negative bacilli, and Staphylococcus aureus. A49759 was two-to fourfold more active than fortimicin A against most species tested, but generally fourfold less active than amikacin against this population of Pseudomonas aeruginosa (85% inhibited at -16 ug of amikacin per ml and 85% inhibited at c64 ,ug of A49759 per ml). Only amikacin and A49759 were resistant to most aminoglycoside-inactivating enzymes and also had significant antipseudomonal activity. Amikacin was inactivated by aminoglycoside 6'-acetyltransferase, and A49759 was inactivated by aminoglycoside 3-acetyltransferase. The minimal inhibitory concentrations of all tested aminoglycosides were increased by augmenting the inoculum size. Several recent reports have described the in vitro antimicrobial activity of the pseudodisaccharide aminoglycoside antibiotics (4-8, 10, 11, 13, 14). Among these new compounds, the fortimicin group has been most extensively tested against recent clinical isolates (7). Numerous chemical and natural modifications of fortimicin have been presented (6,8,10,14,15). Fortimicin aminoglycosides are generally resistant to inactivating enzymes (6, 10, 13), but lack significant inhibitory activity against pseudomonads (6, 7). In recently presented abstracts no ototoxicity and very low renal toxicity for fortimicin A in the animal models were described (C. L

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Section: Discussionmentioning

confidence: 73%

“…The pseudodisaccharide aminocycitols are generally resistant to most bacteria-mediated (3,4,11,(13)(14)(15). Only the AAC(3)-I enzyme (3-N-acetylation) routinely inactivates this series of drugs, as well as gentamicin, netilmicin, and sisomicin.…”

Section: Discussionmentioning

confidence: 99%

Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics

Jones¹,

Thornsberry²,

Barry³

et al. 1980

Antimicrob Agents Chemother

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“…Reaction of 0.27 mol of 11 with 7.5 mmol of base in pure acetonitrile under careful exclusion of moisture (dry box) yields after crystallization 93% rac-13a [ The structures rac-13a -f are substantiated by fully analyzed 'H-NMR spectra ( First information about the regiochemistry of epoxide opening in the tricycles 13 came from the reaction of rac13a with sodium azide (excess NaN3, MgS04, methanol, reflux) (Scheme 4). Continuous monitoring of the reaction progress (TLC, 'H NMR) reveals only one product, which can be isolated after total conversion and crystallization with at least 95% yield and is identified as 14a 2p,3f5,4~(,6P I ent-1 ent-20a ent-20b 1733 the le,4a,6e (17**) conformation in the equilibrium with the la,4e,6a conformation (17*) is confirmd i. a. by the generally large coupling constants 558.6 (9.5-12.0 Hz) and 56.1 (7.5 -11.2 Hz) and the long range coupling constants J3,5rr (1)(2)(3). Accordingly, the signals of equatorial 5a-H generally appear at lower field than those of axial 5P-H. After hydrolysis of the carbamate ring in 17alent-17a and 17clent-17c [water/methanol, Ba(OH2)] and acidification with conc.…”

Section: Bausteinementioning

confidence: 91%

Aminoglycoside antibiotics — Enantiomerically pure sannamine building blocks

et al. 1989

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Starting from the prochiral dianhydrodeoxy-epi-inositol 9 a highly efficient synthesis for rac-sannamines (1, salts, derivatives) and rue-de-0-methylsannamine (18, salt) has been developed. Key steps are two regiospecific, practically quantitative epoxide opening reactions: intramolecularly in the diepoxyurethanes 11 and intermolecularly in the epoxyurethanes roc-13. With (R)-1 -phenylethylamine as potential primary amino group in the second step separation of the corresponding diastereomers (16,16') is achieved without significant loss of material. By this route enantiomerically pure (de-0-methy1)sannamines become available in which all functionalities are protected except that to be glycosidated. Attempts for an asymmetric realization of this synthesis resulted in only very small ee(de) values.Sannamine (1) (2-deoxyfortamine) and sporamine (2) are the aglycon building blocks') of a new class of aminoglycoside antibiotics (sannamycins*), istamycins3', sporaricins4'). Their structure is closely related to fortamine (3), the aglycon component of the fortimicins (astromicins)". Reduced side effects and activity towards resistent strains of bacteria are characteristic of this group of antibiotics. A pecularity is their relatively simple pseudo disaccharide structure -with only one sugar (purpurosamine) and one non-sugar component, making synthetic activities in this area particularly attractive. (-1-3In recent years several total syntheses for the aglyca 1 -3 (in brackets antibiotics numbering) starting from racemic o r chiral material were published6' -including the detailed protocol of our own access to enantiomerically pure (de-0-methy1)fortamines". The paper presented here summarizes our activities in the sannamine area'), the subsequent paper*' the results of a n investigation in the sporamine

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Polyfunktionalisierte Cyclohexane aus Dianhydrodesoxyinositen. cis‐Desoxy‐1,3(1,4)‐inosadiamine aus Benzol

et al. 1984

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Durch kontrollierte NBS-Bromierung von 4,5-Epoxycyclohexen (5) wird in 87 -90proz. Ausbeute ein ca. 9: I-Gemisch der (la,2a,6a)-/(la,2~,6a)-2-Brom-7-oxabicycIo[4.1 .O]hept-3-ene (7a/8a) erhalten. Diese kdnnen in Gegenwart von Tetraalkylammoniumbromiden verlustfrei und je nach Polaritat des Losungsmittels zu unterschiedlichen Gemischen (3 : 7 in Acetonitril) aquilibriert und chromatographisch rein isoliert werden. Durch selektive Halogensubstitution (7b/8b, 9 b -d/ 10b -d) und Ammonolyse werden in hohen Ausbeuten die Allylepoxyalkohole 9a/10a zuganglich. Uber die stereospezifische Epoxidierung von 7a/8a gewinnt man die (la,2a,3a,5a,7a)-/ (la,2f5,3a.5a,7a)-Diepoxybromide 12a/14a, die sich ebenfalls verlustfrei aquilibrieren (ca. 9: 1 in CCI,. ca. (1 a,2a,3a,5a,7a)-/(la,2~,3a,5a,7a)-diepoxy bromides 12a/14a. The latter are equilibrated quantitatively to mixtures favoring either one in the ratio of ca. 9: 1 (CCI,) and 1 : 9 (CH,CN), respectively. Upon SN2 substitution with ammonium acylates (+ 13b,c/15 b,c) and ammonolysis the naturally not occurring dianhydrodeoxyinositols 13a/15a are isolated in practically quantitative yields. The usefulness of 13a/15a and of various derivatives for the stereoselective synthesis of cis-1,4-and cis-1,3-disubstituted cyclohexanetriols is exemplified by reactions with monovalent (H,O, HI, NaN,) and divalent nucleophiles (NH,NH,, CH3NHNH2). I . a. the cis-deoxy-l,3-inosadiamines 1 (2-deoxystreptamine)/Z and the cis-deoxy-1 ,Cinosadiamines 3/4 become available in high yields.

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New aminoglycoside antibiotics, sannamycin.

Cited by 24 publications

References 6 publications

Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics

Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics

Aminoglycoside antibiotics — Enantiomerically pure sannamine building blocks

Polyfunktionalisierte Cyclohexane aus Dianhydrodesoxyinositen. cis‐Desoxy‐1,3(1,4)‐inosadiamine aus Benzol

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